BRAF- and MAP2K1-Negative Multisystem Langerhans Cell Histiocytosis in an Elderly Patient
Year: 2023
Type: article
Study design: Case Report
Abstract: Sir, Langerhans cell histiocytosis (LCH) is most commonly seen in children one to three years of age. Skin involvement may manifest as papules, vesicles, pustules, nodules, or ulcers and may be difficult to diagnose. LCH in adults is uncommon, with a prevalence of ~1–2 cases/million.[1] BRAF mutation is present in 40%–70% of patients and MAP2K1 is more common in BRAF-negative patients.[2] We herein report a rare case of BRAF- and MAP2K1-negative LCH in an elderly person with multisystem involvement. A 68-year-old male with hypertension and diabetes insipidus presented to the dermatology clinic with multiple discrete-to-confluent erythematous, itchy, oozy, crusted papules over the trunk and face and macerated, foul-smelling plaques over flexures [Figure 1] for three years and intermittent serous discharge from the right ear for two years. Examination revealed non-tender, freely mobile significant lymphadenopathy involving both the axilla and left inguinal region, pedal oedema, and hepatosplenomegaly. The right ear showed mucoid discharge with anteroinferior-central tympanic membrane perforation. Investigations revealed normocytic normochromic anaemia (haemoglobin level: 10.7 g/dL) and mildly raised bilirubin, gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Skin biopsy showed focal ulceration of epithelium with dense inflammation in superficial and reticular dermis with epidermotropism; sheets of Langerhans cells with abundant, pale eosinophilic cytoplasm; irregular, elongated nuclei with prominent nuclear grooves; fine chromatin and indistinct nucleoli with a characteristic ‘coffee bean’ appearance. Immunohistochemistry revealed strongly positive CD1a and Langerin [Figure 2]. Magnetic resonance imaging (MRI) of the brain revealed absent bright spot with thickened pituitary stalk; Contrast-enhanced computed tomography (CECT) of the abdomen showed splenomegaly with mesenteric infiltration; and positron emission tomography computed tomography (PET-CT) of the whole body showed axillary and mediastinal lymph node enhancement, bilateral pleural effusion, and irregular skin thickening of inguinoscrotal and perianal regions [https://links.lww.com/IJOD/A42]. There was bilateral mastoiditis on high-resolution computed tomography (HRCT) of the temporal bone and concentric left ventricle hypertrophy with mild aortic regurgitation and pericardial effusion on 2D-echo. Bone marrow studies revealed erythroid hyperplasia and BRAFV600E and MAP2K1 mutations were negative. He was diagnosed as LCH with multisystem involvement and was managed with topical corticosteroids (TCS), antibiotics, and cladribine infusion at 9 mg (5 mg/m2)/day × 5 days/month for three cycles. Follow-up at 12 weeks showed remarkable improvement of skin lesions [Figure 3] and other systemic findings. Last follow-up at 52 weeks did not reveal any new disease activity.Figure 1: Multiple discrete-to-confluent erythematous crusted papules over the trunk and neck (a); and macerated erythematous plaques over the axilla, groin, and perianal region (b–d)Figure 2: Focal ulceration of lining epithelium with dense underlying inflammation in superficial and reticular dermis (H&E, 40×) (a); sheets of Langerhans cells with abundant pale eosinophilic cytoplasm, irregular, elongated nuclei with prominent nuclear grooves, and fine chromatin and indistinct nucleoli (H&E, 400×) (b); and immunohistochemistry (IHC) showing strong cytoplasmic Langerin positivity (IHC, 200×) (c); and strong cytoplasmic CD1a positivity (IHC, 400×) (d)Figure 3: Follow-up at 12 weeks showing remarkable improvement in skin lesions over the trunk and chest (a); axilla (b); groin (c); and perianal region (d)Although LCH predominantly affects children, it can affect any age.[3] Cutaneous lesions may at times be the only sign of LCH, with recalcitrant seborrheic dermatitis–like lesions over the scalp and flexural regions being the most common presentation.[4] Bone and lung are the most commonly involved organs, as seen in our case. The most prevalent endocrine symptom is diabetes insipidus which was also observed in our patient.[5] MAP2K1 is the most common mutation in BRAFV600E-negative LCH patients; however, our patient lacked both, which is uncommonly reported. Management is determined by the severity and organs involved. Isolated skin lesions may rarely heal on their own or respond to TCS or nitrogen mustard treatment. Multisystem disease requires chemotherapeutic agents such as vinblastine, vincristine, cladribine, methotrexate, and etoposide. We used cladribine monotherapy in consultation with the haemato-oncologist, with excellent response. We report this case for its rarity in the elderly population and to emphasize the role of the dermatologist in early diagnosis and thereby reducing morbidity and mortality associated with LCH. Management of the disease requires a multi-disciplinary approach, especially involving the dermatologist, haematologist, and pulmonologist based on the organs involved. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgement The patient in this manuscript has given written and informed consent for the publication of his case details and photographs.
Source: Indian Journal of Dermatology
Institution: Command Hospital Air Force
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4375855679